A Phase I Study of ABT-888 in Combination With Conventional Whole Brain Radiation Therapy (WBRT) in Cancer Patients With Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00649207
Recruitment Status : Completed
First Posted : April 1, 2008
Last Update Posted : November 21, 2017
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Brief Summary:
This Phase I clinical trial is studying the side effects and best dose of ABT-888 when given together with Whole Brain Radiation Therapy (WBRT) in treating patients with brain metastases.

Condition or disease Intervention/treatment Phase
Brain Diseases Brain Neoplasms Central Nervous System Diseases Neoplasm Metastasis Nervous System Neoplasms Drug: ABT-888 Radiation: Whole Brain Radiation Therapy Phase 1

Detailed Description:
This is a Phase 1, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of the PARP inhibitor ABT-888 in combination with conventional whole brain radiation therapy (WBRT) in the treatment of subjects with solid tumors metastatic to the brain.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of ABT-888 in Combination With Whole Brain Radiation Therapy in Subjects With Brain Metastases
Study Start Date : March 2008
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Arm Intervention/treatment
Experimental: 1

This is an open label study; therefore, there are no numbered/labeled study arms.

This is a dose escalation study, ABT-888 dose will be escalated in conjunction with two schedules of whole brain radiation therapy (WBRT). Subjects may be treated WBRT for 3 weeks (15 days) or 2 weeks (10 days).

Drug: ABT-888
Oral Capsules
Other Name: veliparib

Radiation: Whole Brain Radiation Therapy
15 fractions of 2.5 Gy over 3 weeks to a total dose of 37.5 GY or 10 fractions of 3.0 Gy over 2 weeks to a total dose of 30 Gy
Other Name: WBRT

Primary Outcome Measures :
  1. Determine the maximum tolerated dose of ABT-888 in combination with whole brain radiation therapy [ Time Frame: ABT-888 will be dose escalated until the largest dose is reached that is felt to be safe based on safety information from all subjects. ]

Secondary Outcome Measures :
  1. Safety Assessment Physical and Neurological Exam [ Time Frame: be performed at all study visits, final and follow-up visit ]
  2. Safety Assessment Mini-Mental State Examination [ Time Frame: be performed at all study visits, final and follow-up visit ]
  3. Safety Assessment Laboratory testing [ Time Frame: be performed at all study visits, final and follow-up visit ]
    Chemistry and Hematology labs will be collected

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age is greater than or equal to 18 years.
  • Histologically or cytologically confirmed non-CNS primary solid malignancy.
  • Pathologically or radiographically confirmed metastatic disease in the brain. Subjects with non-measurable lesions, including leptomeningeal carcinomatosis, are eligible.
  • WBRT is clinically indicated, with the exception of prophylactic treatment.
  • Karnofsky Performance Status (KPS) greater than or equal to a score of 70.
  • Adequate hematology, renal and hepatic function.
  • Both men and women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 2 months following completion of protocol therapy.

    • Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
    • A vasectomized partner * Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
    • Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
  • Subject is capable of understanding and complying with parameters as outlined in the protocol.
  • Subject or the subject's legally acceptable representative has voluntarily signed and dated the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  • Brain metastases secondary to germ cell tumor or lymphoma malignancy.
  • Primary central nervous system (CNS) neoplasm.
  • Prior or concurrent administration of the following therapies or treatments:

    • Prior treatment with WBRT
    • SRS performed less than 14 days prior to WBRT D1, or is scheduled to occur within 30 days of the last WBRT session
    • Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy was less than 14 days prior to WBRT D1. Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment.
  • Known seizure disorder (status epileptics) that is uncontrolled, or seizures occurring greater than or equal to 3 times a week over the past month.
  • If female, subject is pregnant or breast-feeding.
  • Clinically significant and uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder, including but not limited to:

    • Active uncontrolled infection
    • Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
    • Any other illness condition(s) that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit compliance with study requirements
  • Unable to swallow and retain oral medications.
  • Known contraindication to enhanced MRI and CT, including but not limited to:

    • Presence of metal objects within the body such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel
    • History of immediate or delayed hypersensitivity reaction or other contraindication to contrast agents including but not limited to gadolinium and iodine
  • Previous enrollment in this study or another study involving the investigation of ABT-888, with the exception of receiving a single dose of study drug.
  • Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-888 and/or WBRT.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00649207

United States, Georgia
Site Reference ID/Investigator# 8334
Atlanta, Georgia, United States, 30322
United States, Illinois
Site Reference ID/Investigator# 52462
Chicago, Illinois, United States, 60611
United States, Kansas
Site Reference ID/Investigator# 24483
Kansas City, Kansas, United States, 66160
United States, Maryland
Site Reference ID/Investigator# 7180
Baltimore, Maryland, United States, 21231-2410
United States, Michigan
Site Reference ID/Investigator# 19021
Detroit, Michigan, United States, 48202-2689
United States, Pennsylvania
Site Reference ID/Investigator# 6344
Philadelphia, Pennsylvania, United States, 19111
United States, Wisconsin
Site Reference ID/Investigator# 6653
Madison, Wisconsin, United States, 53792
Site Reference ID/Investigator# 18542
Toronto, Canada, M5G 2M9
Puerto Rico
Site Reference ID/Investigator# 46322
Ponce, Puerto Rico, 00716
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Study Director: Shepherd L Stacie, MD AbbVie

Publications of Results:
Responsible Party: AbbVie (prior sponsor, Abbott) Identifier: NCT00649207     History of Changes
Other Study ID Numbers: M10-128
First Posted: April 1, 2008    Key Record Dates
Last Update Posted: November 21, 2017
Last Verified: May 2013

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):
Brain Metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Nervous System Diseases
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Neoplasms by Site
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents